High performance liquid chromatography station for rapid reaction analysis and optimization

用于快速反应分析和优化的高效液相色谱站

• 批准号: 359465-2008
• 负责人: OrellanaGarcia, Josue
• 金额: $ 6.51万
• 依托单位: York University
• 依托单位国家: 加拿大
• 项目类别: Research Tools and Instruments - Category 1 (<$150,000)
• 财政年份: 2007
• 资助国家: 加拿大
• 起止时间: 2007-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=365452
• 关键词: performance; liquid; chromatography; station; rapid

The proposed research has as its overarching aim the provision of synthetic solutions to problems of molecular complexity by developing new reactions using molecular rearrangements as key design elements.  The approach to these problems will be twofold:  i) we will target complex natural products with important biological properties, and ii) we will develop new complexity generating reactions that should be widely useful to the synthetic community.Specifically, we will develop a synthesis of cortistatin A, an important natural product and potential lead for the development of anticancer-therapeutics.  To carry out this synthesis, a new cascade reaction has been designed to deal with some of the central structural issues present in the target compound.  Successful completion of this work will allow biological evaluation for anti-angiogenic activity (in collaboration with Professor Tara Haas of York University).In addition, we are interested in developing complexity-generating reactions using sequential molecular rearrangements.  These reactions are expected to have wide application by the community since they provide access to enantioenriched polysubstituted chiral carbocyclic, heterocyclic and acyclic compounds.Crucial to our work is the rapid analysis of multiple reactions in support of optimization.  HPLC analysis has supplanted other more time-consuming and less accurate techniques as the standard method of analysis.  The HPLC station requested will have a significant impact on the success of our reasearch.

提出的研究的总体目标是通过开发以分子重排为关键设计元素的新反应，为分子复杂性问题提供合成解决方案。解决这些问题的方法将是双重的：i)我们将以具有重要生物学特性的复杂天然产物为目标，ii)我们将开发新的复杂生成反应，这些反应应该对合成界广泛有用。具体来说，我们将开发一种合成皮质抑素a，这是一种重要的天然产物，也是抗癌治疗药物发展的潜在先导。为了进行这种合成，设计了一种新的级联反应来处理目标化合物中存在的一些中心结构问题。这项工作的成功完成将允许对抗血管生成活性进行生物学评估（与约克大学的Tara Haas教授合作）。此外，我们对开发使用顺序分子重排的复杂生成反应感兴趣。这些反应为制备对映体富集的多取代手性碳环、杂环和无环化合物提供了途径，有望得到广泛的应用。对我们的工作至关重要的是多种反应的快速分析，以支持优化。高效液相色谱分析已经取代了其他耗时和不准确的技术作为标准的分析方法。所要求的HPLC站将对我们的研究成功产生重大影响。